Download a peptide specialist

POLYPEPTIDE LABS PHOTO
WET OR DRY PolyPeptide uses solution-phase methods, shown here, and
solid-phase techniques to synthesize peptides at its Torrance, Calif., facility.
A PEPTIDE SPECIALIST
PolyPeptide Laboratories sticks to what it
knows in pharmaceutical chemicals
M I C H A E L M C C OY , C & E N N O R T H E A S T N E W S B U R E A U
ven in the specialized world
of pharmaceutical chemical production, PolyPeptide Laboratories stands out. The company operates five facilities in the U.S.
and Europe, all of which are focused on
just one thing: pharmaceutical peptide
manufacturing.
PPL’s devotion to this area of expertise
seems to be paying off. The company is
generally regarded as one of the world’s top
three bulk peptide producers, and it so far
has survived an onslaught by larger multipurpose fine chemicals companies that see
peptides as an attractive niche in a mostly
slow-growing field.
PPL can trace its history back to the
1950s, when drug companies began extracting natural peptides such as adrenocorticotropic hormone (ACTH) from animal organs. Later came peptide synthesis
through the solution- and solid-phase coupling of amino acids into peptide chains
of up to 45 links.
PPLwas formally created in 1996 when
the European peptide synthesis arms of
two drugmakers joined and became an independent firm. Soon, two other European facilities were brought into the group,
and a U.S. unit was formed by Jane Salik,
then a vice president at peptide manufac-
E
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turer Bachem California, and her colleagues, the peptide chemistry experts Nagana A. Goud and Michael Verlander.
Today, the PPLGroup is a privately held
company that employs more than 300 people worldwide. Salik, who is president of
PPL’s U.S. operation in Torrance, Calif., and
is on its executive management board, says
the group’s annual sales exceed $80 million, making it by her reckoning the number two peptide manufacturer after
Switzerland-based Bachem.
Salik says PPL’s sales have been growing
at double-digit rates in recent years, a fact
she attributes both to her firm’s successful
manufacturing track record and to a new
wave of peptide therapeutics that are coming through drug company labs and starting to hit the market.
“Not only are peptide projects interesting to smaller biotech firms, but big
pharmaceutical companies are looking at
peptides as well,” she says. Moreover,
whereas large firms traditionally entered
peptide therapeutics via partnerships with
a biotech company, they are increasingly
getting involved on their own, she adds.
In addition to ACTH, the first wave of
peptides included calcitonin, an osteoporosis drug; oxytocin, used to induce labor and one of the first chemically synC & E N / J U LY 1 8 , 2 0 0 5
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thesized peptides; and desmopressin, a
treatment for excessive thirst or urination.
Although peptide therapeutics boast
advantages such as high potency and low
toxicity, a big drawback is that most must
be administered by injection. As a result,
patient compliance problems emerged in
the 1990s that caused drug industry interest in the field to wane somewhat.
More recently, though, new controlledrelease, nasal, and inhaled delivery forms
have made peptides more palatable to patients. AstraZeneca’s Zoladex LA, for example, is a cancer therapy that can be injected once every three months because
its peptide ingredient, goserelin, is wrapped
in a slowly biodegrading polymer.
Rodney Lax, PPL’s director of sales and
marketing, also credits the approval and
large-scale manufacture of Fuzeon, a peptide-based HIV treatment developed by
Trimeris and Roche, for boosting peptide
awareness. “The Fuzeon project has helped
companies to recognize that big peptides
can be economically manufactured on a very
substantial scale,” Lax says. The sheer quantity of raw materials consumed by Roche at
its Boulder, Colo., plant—more than 100
tons per year—has also helped bring down
prices of peptide raw materials, he adds.
OF COURSE, nothing attracts drug companies like potentially large markets. The
early peptides were either hormones or
closely related to hormones, and thus tended to treat exotic endocrine disorders or
endocrine-dependent cancers. Today, Salik
says, peptides are in development in almost
every drug category, including anti-inflammatory, gastrointestinal, and antiobesity.
One peptide developer—and PPL customer—is Zelos Therapeutics, which is
developing Ostabolin C for treatment of
osteoporosis and psoriasis, both multi-billion-dollar markets. Spun off in 2000 from
Canada’s National Research Council
(NRC), Zelos has raised close to $60 million in venture capital.
Paul Morley was studying the chemistry
and biology of parathyroid hormone at
NRC in the mid-1990s when he and his colleagues realized that analogs of the hormone
had the potential to treat osteoporosis. He
joined the Zelos spin-off, becoming chief
technical officer, and soon embarked on a
search for a manufacturer that could produce the peptide to current Good Manufacturing Practices (cGMP) standards.
According to Morley, Zelos immediately gravitated toward the “big three” in peptide manufacturing—PPL, Bachem, and
UCB Bioproducts—because it wanted to
work with a single firm that could be its
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partner from laboratory-scale production
all the way through Phase II and Phase III
manufacturing.
Morley says he liked PPL’s long experience with peptide chemistry and the fact
that it could produce in multiple countries.
But mostly, he says he liked PPL employees such as Verlander, who has 25 years of
experience in peptide manufacturing.
“There’s not really rocket science involved,” he says of peptide manufacturing.
“These are standard solid-phase synthetic
mechanisms being used, and it’s a matter
of trying the right approaches to get the
yields and efficiencies that you need.”
Zelos’ experience with PPL since then
has been favorable, Morley reports. Ostabolin C recently entered a Phase II clinical trial with a PPL-made product, and PPL
has completed development of a manufacturing process that can take the compound,
which contains 31 amino acids and features
a lactam bridge, to commercial launch. Separately, Zelos is working with the drug delivery firm Nektar Therapeutics to develop
an inhalable powder form of its peptide.
Thanks to the needs of customers like
Zelos, PPL is in the process of expanding
peptide production capacity at its cGMP
plants in California and Malmö, Sweden.
By 2006, Salik says, the “multi-milliondollar” projects should boost U.S. capacity by more than 30% and Swedish capacity by almost that much.
PPLisn’t the only company investing in
peptide manufacturing, however. Fine
chemicals giant Lonza recently announced
it will spend $20 million to add to peptide
capacity in Visp, Switzerland. And companies like UCB and SNPE’s NeoMPS unit
have been expanding as well.
For Lonza and some other multipurpose pharmaceutical chemical companies,
peptides go hand-in-hand with oligonucleotides, a family of therapeutics made by
combining nucleotides just as amino acids
are linked in peptides. Oligonucleotides
are at the heart of drugs in currently popular research fields such as antisense,
RNAi, and siRNA.
According to Lax, PPL’s management
board has tossed around the idea of entering oligonucleotide manufacturing. “The
chemistry is very similar, so there’s no reason why we couldn’t do it,” he says.
Management, however, might want to
consider the opinion of Zelos’ Morley, who
likes the fact that PPL is a specialist’s specialist. “When the lure of oligos and antisense and siRNAcame along, PolyPeptide
didn’t change,” he says. “They were formed
on their expertise in peptides, and they
stuck with that.” ■
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